Our research is concerned with mechanisms of the regulation and control of wound healing. Understanding these mechanisms is of importance not only to basic biology but to those fields of clinical medicine concerned with cell growth and wound healing. In connection with this goal we have isolated a growth factor, mesodermal growth factor (MGF), which is a potent mitogen for corneal fibroblasts and endothelial cells. We have developed methods for evaluating the biological activities of this growth factor in three systems: tissue culture, organ culture, and living animals. Tissue culture methods afford a means for determining its mechanism of action and for evaluating potential cofactors such as corticosteroids, ascorbic acid, and insulin. Our organ culture method permits a study of the growth factor under completely controlled conditions in tissues which retain their normal morphological and tissue-to-tissue relationships with their potential interactions. The stimulation of cellular hypertrophy and cell division produced in vivo by the growth factor permits the development of animal models for evaluation of its effects in clinically oriented problems. MGF greatly accelerates the nromal healing of non-penetrating knife wounds of the rabbit cornea in vivo. We have recently shown that MGF stimulates healing of freeze-thaw injuries to the corneal endothelium in both rabbits and humans in organ cultures of whole corneas. These studies will be extended to include healing of cat endothelium in vivo, since cat endothelium is believed to more closely resemble the healing of human endothelium than does that of the rabbit. We will explore basic mechanisms of corneal endothelial wound repair using the organ culture system described above. Human and cat endothelium show unexplained regenerative capacities in vitro greatly exceeding those in vivo. We plan to investigate sgme possibilities we have uncovered that may account for the difference.